Review Article

Trends and Advances in Separation and Detection of SSRIs and SNRIs in Biological Matrices

Table 1

Liquid chromatographic methods developed for detection of SSRIs, SNRIs, and their metabolites.

MatrixAnalyteExtraction methodDetector systemSensitivityReferences

Mass detector
PlasmaSER and N-DSERLLETMSLOQ = 0.5 ng/mL[21]
PlasmaFLX and NFLXLLEESI, SIM*LOQ = 2.5  g/mL for FLX and 10  g/mL NFLX[25]
PlasmaFLXSBSEESI, SIMLOQ = 30 pg/mL (liquid desorption) and 1.37 pg/mL (thermal desorption)[26]
HairCIT, DCIT, and DDCITLLETMSLOD = 10 pg/mg
LOQ = 20 pg/mg
[33]
PlasmaVLF, O-DVLF, N-DVLF
N,O-didesmethylvenlafaxine (DDVLF)
LLEMSLOD = 0.4, 0.2, 0.3, and 0.2 ng/mL and
LLOQ = 3.5, 2.2, 2.7, and 1.9 ng/mL for
VLF, O-DVLF, N-DVLF, and DDVLF, respectively
[75]
PlasmaSERSPETriple stage
(ESI, SRM)
LOQ = 0.5 ng/mL[76]
Oral fluid and plasmaFLX, NFLX PAR, SER, FLV, CIT, and VLF Automated SPETMS (ESI), with triple quadrupoleLOQ = 2 ng/mL in oral fluid, 2 ng/mL in plasma (except FLV 10 ng/mL and NFLX 4 ng/mL)[77]
PlasmaFLX and NFLXAutomated SPETriple stage
(ESI, SRM)
LLOQ = 0.5 ng/mL [78]
PlasmaFLX and NFLXOnline extraction using column switchingESI, SIMLOQ = 25 ng/mL[79]
PlasmaVLF and -DVLFSPETMS, SRMLOQ = 3 ng/mL for VLF, 6 ng/mL for DVLF[80]
PlasmaCITLLEESI, SIM LOQ = 0.50 ng/mL[81]
PlasmaCIT and DCITDeproteinizationMS (SIM)LOQ = 0.25 to 0.5 ng/mL[82]
PlasmaFLV, PAR, and MCPSPEQMS-(SSI)*LOD = 0.05 to 0.13  g/mL and LOQ = 0.10 to 0.20  g/mL[83]
PlasmaFLX and NFLXLLETMS (ESI)LOQ = 0.15 ng/mL[84]
PlasmaFLX, CIT, PAR, and VLFSPEMS (ESI)LOD, FLX = 0.5, CIT = 0.3, PAR = 0.3, and VEN = 0.1 ng/mL[85]
BloodFLX, PAR, SER, FLV, CIT, VLF, NFLX, DCIT, DDCIT, and DVLFLLETMSLOD = 5–500 ng/mL and LOQ = 5 ng/mL
LOD = 20–2000 ng/mL for VLF and DVLF 
LOQ = 20 ng/mL for VLF and DVLF
[86]

UV detector
Urine and plasmaSERHF-LPMEUVLOD = 0.5  g/L
LOQ = 2.3  g/L
[18]
PlasmaCIT and DCITLLEUVLOD = 5 ng/mL [38]
PlasmaCIT, SER, FLX, PAR, and DLXSBSEUVLOD = 20 ng/mL for CIT and PAR, 25 ng/mL for FLX and SER and 16 ng/mL for DLX[44]
PlasmaFLX, SER, PAR, and CITLLEUVLOQ = 10 ng/mL for FLX, SER, and PAR and 5 ng/mL for CIT[87]
Plasma and urineFLX, PAR, and VLFSPEUVLOD = 0.2–0.6 ng/ L in plasma and 0.1–0.8 ng/ L in urine [88]
PlasmaCIT, FLX, PARSPEUVLOQ = 0.05 to 0.26 mM[89]
PlasmaCIT, DCIT, DDCIT, FLV, PAR, SER,
FLX, NFLX, VLF, and
O-DVLF
LLEUVLOQ = 25 ng/mL, 100 ng/mL for VLF and O-DVLF[90]
PlasmaR- and S-CIT, R- and S-DCIT, and R- and S-DDCITLLEUVLOD > 2 ng/mL[91]
Fluorescence detector
PlasmaFLX and NFLXLLEFDLLOD = 3 mg/L[17]
PlasmaSER and DSER SPEFDLOQ = 1.0 ng/mL and LOD = 0.3 ng/mL[22]
PlasmaCIT, DCIT, DDCITSPEFDLOQ = 1.5 to 2 ng/mL [32]
Plasma, urine, and brain tissueCIT, DCIT, DDCIT, FLX, NFLX, VLF, and
O-DVLF
SBSEFDLOQ = 0.2 to 2 mg/L in plasma, 2 to 20 ng/g in brain tissue, and 1 to 10 mg/L in urine[49]
SerumSERLLEFDLOQ up to 2 ng/mL[53]
PlasmaCIT, DCIT, DDCIT, PAR, and PAR metabolitesSPEFDLOQ = 0.025 to 0.12 mmol/L[92]
SerumCIT, FLX, and NFLXLLEFDLOQ = 50 mg/L [93]
PlasmaFLX and NFLX HF-LPMEFDLOQ = 5 ng/mL[89]
PlasmaCIT, DCIT, and DDCITSPEFDLOD = 0.8 nmol/L[94]

Diode array detector
PlasmaFLX, NFLX, SER, PAR, CIT, FLV, VLF, MCP, and DVLFLLEDADLOD = 2.5 to 5 ng/mL[95]
UrineCIT, DCIT, DDCIT, FLX, and NFLXSPMEDADLOD = 0.01–0.09 mg/L[96]

Abbreviations*: SIM: Single Ion Monitoring; QMS: Quadrupole Mass Spectrometry; SSI: Sonic Spray Ionisation.